Caracterización funcional y clínica del epcr como gen prometastásico en el adenocarcinoma de pulmón

Abstract

The EPCR receptor and its ligand APC have been implicated in the anticoagulant activity of endothelial cells but their role in human cancer remains largely unknown. The aim of this study was to elucidate the function of EPCR in lung adenocarcinoma. Abrogation of EPCR expression in lung cancer cell lines, by using two lentiviral knock down constructs dramatically reduced prometastatic activity to the bone compartment. Similarly, blocking antibodies preventing EPCR-APC interaction, showed similar antimetastatic activity. These results were associated with impaired bone homing activity. As expected, EPCR overexpression in lung cancer cells showed an increased metastatic activity. Moreover, immunohistochemical analysis in a large cohort of lung cancer patients revealed a marked association between high EPCR levels and poor survival or relapse in patients with stage I lung adenocarcinoma. In these patients EPCR was an independent pronostic factor. Thus our results suggest that patients with stage I adenocarcinoma and high EPCR may benefit from adjuvant therapy. Future studies will dissect the molecular mechanisms triggered by EPCR-APC in promoting lung adenocarcinoma dissemination.